Abstract:
:The HER4 intracellular domain (4ICD) is a potent estrogen receptor (ERalpha) coactivator with activities in breast cancer and the developing mammary gland that appear to overlap with progesterone receptor (PgR). In fact, 4ICD has recently emerged as an important regulator and predictor of tamoxifen response, a role previously thought to be fulfilled by PgR. Here we investigated the possibility that the 4ICD coactivator regulates PgR expression thereby providing a mechanistic explanation for their partially overlapping activities in breast cancer. We show that 4ICD is both sufficient and necessary to potentiate estrogen stimulation of gene expression. Suppression of HER4/4ICD expression in the MCF-7 breast tumor cell line completely eliminated estrogen stimulated expression of PgR. In addition, the HER4/4ICD negative MCF-7 variant, TamR, failed to express PgR in response to estrogen. Reintroduction of wild-type HER4 but not the gamma-secretase processing mutant HER4V673I into the TamR cell line restored PgR expression indicating that 4ICD is an essential PgR coactivator in breast tumor cells. These results were substantiated in vivo using two different physiologically relevant experimental systems. In the mouse mammary gland estrogen regulates expression of PgR-A whereas expression of PgR-B is estrogen independent. Consistent with a role for 4ICD in estrogen regulated PgR expression in vivo, PgR-A, but not PgR-B, expression was abolished in HER4-null mouse mammary glands during pregnancy. Coexpression of PgR and 4ICD is also commonly observed in ERalpha positive breast carcinomas. Using quantitative AQUA IHC technology we found that 4ICD potentiated PgR expression in primary breast tumors and the highest levels of PgR expression required coexpression of ERalpha and the 4ICD coactivator. In summary, our results provide compelling evidence that 4ICD is a physiologically important ERalpha coactivator and 4ICD cooperates with ERalpha to potentiate PgR expression in the normal and malignant breast. We propose that direct coupling of these signaling pathways may have important implications for mammary development, breast carcinogenesis, and patient response to endocrine therapy.
journal_name
Mol Cancerjournal_title
Molecular cancerauthors
Rokicki J,Das PM,Giltnane JM,Wansbury O,Rimm DL,Howard BA,Jones FEdoi
10.1186/1476-4598-9-150subject
Has Abstractpub_date
2010-06-15 00:00:00pages
150issn
1476-4598pii
1476-4598-9-150journal_volume
9pub_type
杂志文章相关文献
Molecular Cancer文献大全abstract:BACKGROUND:Sigma-2 receptors are over-expressed in proliferating cancer cells, making an attractive target for the targeted treatment of pancreatic cancer. In this study, we investigated the role of the novel sigma-2 receptor ligand SW43 to induce apoptosis and augment standard chemotherapy. RESULTS:The binding affini...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-298
更新日期:2010-11-22 00:00:00
abstract:BACKGROUND:The transcription factor Runx2 has an established role in cancers that metastasize to bone. In metastatic breast cancer cells Runx2 is overexpressed and contributes to the invasive capacity of the cells by regulating the expression of several invasion genes. CBFbeta is a transcriptional co-activator that is ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-171
更新日期:2010-06-30 00:00:00
abstract:BACKGROUND:The clinical efficacy of camptothecin (CPT), a drug specifically targeting topoisomerase I (TopoI), is under evaluation for the treatment of malignant gliomas. Due to the high unresponsiveness of these tumours to chemotherapy, it would be very important to study the signalling network that drives camptotheci...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-7-66
更新日期:2008-08-11 00:00:00
abstract:BACKGROUND:The pre-leukemia transcription factor 3 (PBX) is part of the PBX family of transcription factors, which is known to regulate genes involved in differentiation of urogenital organs and steroidogenesis. This is of interest with regard to prostate cancer progression as regulation of steroidogenesis is one of th...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-10-50
更新日期:2011-05-06 00:00:00
abstract:BACKGROUND:Alterations of chromosome 8 and hypomethylation of LINE-1 retrotransposons are common alterations in advanced prostate carcinoma. In a former study including many metastatic cases, they strongly correlated with each other. To elucidate a possible interaction between the two alterations, we investigated their...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-6-14
更新日期:2007-02-05 00:00:00
abstract:BACKGROUND:To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC). PATIENTS AND METHODS:We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In addition, 21 larynx, 10 orop...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-106
更新日期:2010-05-12 00:00:00
abstract:BACKGROUND:Fusion of the MOZ and TIF2 genes by an inv (8) (p11q13) translocation has been identified in patients with acute mixed-lineage leukemia. Characterization of the molecular structure of the MOZ-TIF2 fusion protein suggested that the fusion protein would effect on nuclear receptor signaling. RESULTS:A series o...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-6-51
更新日期:2007-08-13 00:00:00
abstract:BACKGROUND:There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. METHOD:Bioinformatics methods were applied to screen...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-021-01314-w
更新日期:2021-01-20 00:00:00
abstract:BACKGROUND:Colorectal cancers carrying the B-Raf V600E-mutation are associated with a poor prognosis. The purpose of this study was to identify B-RafV600E-mediated traits of cancer cells in a genetic in vitro model and to assess the selective sensitization of B-RafV600E-mutant cancer cells towards therapeutic agents. ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-122
更新日期:2014-05-24 00:00:00
abstract:BACKGROUND:Hypoxia inducible factor-1 alpha (HIF-1alpha) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1alpha protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1alpha RNA and protein in normal ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-8-104
更新日期:2009-11-17 00:00:00
abstract::Live animal imaging is becoming an increasingly common technique for accurate and quantitative assessment of tumor burden over time. Bioluminescence imaging systems rely on a bioluminescent signal from tumor cells, typically generated from expression of the firefly luciferase gene. However, previous reports have sugge...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-299
更新日期:2010-11-22 00:00:00
abstract::Tumor metabolism is a thrilling discipline that focuses on mechanisms used by cancer cells to earn crucial building blocks and energy to preserve growth and overcome resistance to various treatment modalities. At the same time, therapies directed specifically against aberrant signalling pathways driven by protein tyro...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-018-0798-9
更新日期:2018-02-19 00:00:00
abstract:BACKGROUND:Truncated dopamine and cyclic-AMP-regulated phosphoprotein (t-DARPP) is frequently overexpressed in gastrointestinal malignancies. In this study, we examined the role of t-DARPP in regulating β-catenin. RESULTS:The pTopFlash construct that contains multiple TCF/LEF-binding sites was used as a measure of β-c...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-10-32
更新日期:2011-03-29 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with high morbidity and mortality worldwide. To date, limited therapeutic achievements targeting cell proliferation and related mechanisms has led researchers to focus on the microenvironment where pancreatic cancers develop. The anomalous proliferation ...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-018-0927-5
更新日期:2019-01-21 00:00:00
abstract:BACKGROUND:Granulosa cell tumors (GCTs) are relatively rare and are subtypes of the sex-cord stromal neoplasms. Methylation induced silencing in the promoters of genes such as tumor suppressor genes, DNA repair genes and pro-apoptotic genes is recognised as a critical factor in cancer development. METHODS:We examined ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-3-33
更新日期:2004-12-01 00:00:00
abstract:BACKGROUND:Although chemotherapy represents a predominant anti-cancer therapeutic modality, drug treatment efficacy is often limited due to the development of resistant tumor cells. The pregnane X receptor (PXR) affects chemotherapeutic effects by regulating targets involved in drug metabolism and transportation, but t...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-017-0641-8
更新日期:2017-03-29 00:00:00
abstract:BACKGROUND:Fibroblast growth factors FGF-1 and FGF-2 are often upregulated in tumors, but tightly bound to heparan sulphate proteoglycans of the extracellular matrix (ECM). One mechanism of their bioactivation relies on the FGF-binding protein (FGF-BP) which, upon reversible binding to FGF-1 or -2, leads to their relea...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-10-144
更新日期:2011-11-23 00:00:00
abstract::Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important con...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/1476-4598-4-36
更新日期:2005-09-13 00:00:00
abstract:BACKGROUND:TGF-β promotes tumor invasion and metastasis through inducing epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) are recognized as functional non-coding RNAs involved in human cancers. However, whether and how circRNAs contribute to TGF-β-induced EMT and m...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-018-0889-7
更新日期:2018-09-27 00:00:00
abstract:BACKGROUND:Most ovarian cancers are highly invasive in nature and the high burden of metastatic disease make them a leading cause of mortality among all gynaecological malignancies. The homeodomain transcription factor, PITX2 is associated with cancer in different tissues. Our previous studies demonstrated increased PI...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-015-0433-y
更新日期:2015-08-23 00:00:00
abstract::Monoclonal antibodies represent some of the most promising molecular targeted immunotherapies. However, understanding mechanisms by which tumors evade elimination by the immune system of the host presents a significant challenge for developing effective cancer immunotherapies. The interaction of cancer cells with the ...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/1476-4598-9-242
更新日期:2010-09-15 00:00:00
abstract:BACKGROUND:MUC16 is a cell surface mucin expressed at high levels by epithelial ovarian tumors. Following proteolytic cleavage, cell surface MUC16 (csMUC16) is shed in the extracellular milieu and is detected in the serum of cancer patients as the tumor marker CA125. csMUC16 acts as an adhesion molecule and facilitates...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-118
更新日期:2010-05-24 00:00:00
abstract::Since the publication of this work [1] and in response to a recent query that was brought to our attention in relation to the Western Blot in Figure 1(C) for NP2, protein lysates prepared around the same time as those presented in the manuscript in question, were run by SDS-PAGE under similar experimental conditions a...
journal_title:Molecular cancer
pub_type: 已发布勘误
doi:10.1186/s12943-020-1142-8
更新日期:2020-01-27 00:00:00
abstract:BACKGROUND:Though esophageal cancer is three to four times more common among males than females worldwide, this type of cancer still ranks in the top incidence among women, even more than the female specific cancer types. The occurrence is currently attributed to extrinsic factors, including tobacco use and alcohol con...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-019-0949-7
更新日期:2019-02-08 00:00:00
abstract::In recent years, thyroid malignances have become more prevalent, especially among women. The most common sporadic types of thyroid tumors of follicular origin include papillary, follicular and anaplastic thyroid carcinomas. Although modern diagnosis methods enable the identification of tumors of small diameter, tumor ...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-018-0866-1
更新日期:2018-08-08 00:00:00
abstract:BACKGROUND:Phospholipid phosphatase 4 (PPAPDC1A or PLPP4) has been demonstrated to be involved in the malignant process of many cancers. The purpose of this study was to investigate the clinical significance and biological roles of PLPP4 in lung carcinoma. METHODS:PLPP4 expression was examined in 8 paired lung carcino...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-017-0717-5
更新日期:2017-08-29 00:00:00
abstract:BACKGROUND:Human clear cell renal cell carcinoma (CRCC) remains resistant to therapies. Recent advances in Hypoxia Inducible Factors (HIF) molecular network led to targeted therapies, but unfortunately with only limited clinical significance. Elucidating the molecular processes involved in kidney tumorigenesis and resi...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-8-123
更新日期:2009-12-16 00:00:00
abstract::Oncolytic viruses (OVs) are tumor-selective, multi-mechanistic antitumor agents. They kill infected cancer and associated endothelial cells via direct oncolysis, and uninfected cells via tumor vasculature targeting and bystander effect. Multimodal immunogenic cell death (ICD) together with autophagy often induced by O...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/1476-4598-12-103
更新日期:2013-09-11 00:00:00
abstract:BACKGROUND:Lung cancer is the most lethal cancer and almost 90% of lung cancer is due to cigarette smoking. Even though nicotine, one of the major ingredients of cigarette smoke and the causative agent for addiction, is not a carcinogen by itself, several investigators have shown that nicotine can induce cell prolifera...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-220
更新日期:2010-08-20 00:00:00
abstract::Sema4D, also known as CD100, is a protein belonging to class IV semaphorin. Its physiologic roles in the immune and nervous systems have been extensively explored. However, the roles of Sema4D have extended beyond these traditionally studied territories. Via interaction with its high affinity receptor Plexin-B1, Sema4...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/1476-4598-9-251
更新日期:2010-09-21 00:00:00